Neutron source for neutron capture therapy

ABSTRACT

A Boron neutron cancer treatment system has a central treatment chamber for a subject, with six substantially identical neutron generators each having an acceleration chamber, the generators positioned around a secondary moderator with the axis of each acceleration chamber passing through center of the treatment chamber, and with angled sides of the neutron generators fully adjacent.

CROSS REFERENCED TO RELATED APPLICATIONS

This present application is a divisional application of co-pending U.S.application Ser. No. 16/662,523, filed 24 Oct. 2019, which claimspriority to provisional application 62/749,875, filed Oct. 24, 2018, andwhich is a continuation in part (CIP) of U.S. application Ser. No.15/488,983, filed Apr. 17, 2017, which claimed priority to U.S.application Ser. No. 14/190,389, filed Feb. 26, 2014, which has issuedas U.S. Pat. No. 9,636,524 on May 2, 2017, which claimed priority toU.S. application Ser. No. 13/532,447, filed on Jun. 25, 2012, nowabandoned, which claimed priority to provisional U.S. patent application61/571,406 filed Jun. 27, 2011.

BACKGROUND OF THE INVENTION 1. Field of the Invention

This invention is in the technical area of apparatus and methods forBoron Neutron capture therapy for cancer.

2. Description of Related Art

Boron Neutron Capture Therapy (BNCT) is not new in the art, as thermalneutrons have been used for cancer therapy for the destruction of cancertumors. These neutrons interact with boron-10 that has been placed atthe cancer site. The neutrons interact with the boron to produce fissionevents whereby alpha particles and lithium nuclei are created. Thesemassive ionized particles are then released, destroying the chemicalbonds of nearby cancer tumor cells. At present the neutrons created in areactor or accelerator pass through a moderator, which shapes theneutron energy spectrum suitable for BNCT treatment. While passingthrough the moderator and then the tissue of the patient, the neutronsare slowed by collisions and become low energy thermal neutrons. Thethermal neutrons undergo reactions with the boron-10 nuclei at a cancersite, forming compound nuclei (excited boron-11), which then promptlydisintegrate to lithium-7 and an alpha particle. Both the alpha particleand the lithium ion produce closely spaced ionizations in the immediatevicinity of the reaction, with a range of approximately 5-9 micrometers,or roughly the thickness of one cell diameter. The release of thisenergy destroys surrounding cancer cells. This technique is advantageoussince the radiation damage occurs over a short range and thus normaltissues can be spared.

Gadolinium can also be considered as a capture agent in neutron capturetherapy (NCT) because of its very high neutron capture cross section. Anumber of gadolinium compounds have been used routinely as contrastagents for imaging brain tumors. The tumors have absorbed a largefraction of the gadolinium, making gadolinium an excellent capture agentfor NCT. Therefore, GNTC may also be considered as a variation inembodiments of the present invention.

The following definitions of neutron energy ranges, E, are usedfrequently by those skilled in the art of producing and using neutronsfor medical, commercial and scientific applications: Fast (E>1 MeV),Epithermal (0.5 eV<E<1 Mev) and Thermal (E<0.5 eV) neutrons.

BNCT has the potential to treat previously untreatable cancers such asglioblastoma multiforme (GBM). In the US brain tumors are the secondmost frequent cause of cancer-related deaths for males under 29 andfemales under 20. GBM is nearly always fatal and has, until now, noknown effective treatment. There are approximately 13,000 deaths peryear due to primary brain tumors.

If conventional medicine is used where the glioblast is excised, newtumors almost invariably recur, frequently far from the original tumorsite. Effective radiation therapy, therefore, must encompass a largevolume and the radiation must be uniformly distributed. Conventionalradiation treatment is usually too toxic to be of use against GBM.

For distributed tumors, effective radiation therapy must encompass alarger volume and the radiation must be uniformly distributed. This isalso true of liver cancers. The liver is the most common target ofmetastases from many primary tumors. Primary and metastatic livercancers are usually fatal, especially after resection of multipleindividual tumors. The response rate for nonresectable hepatocellularcarcinoma to traditional radiation treatment or chemotherapy is alsovery poor. However, recent results indicate that the thermal neutronirradiation of the whole liver with a ¹⁰B compound, to be bombarded withlow-energy neutrons, could be a way to destroy all the liver metastases.

Recent research in BNCT has shown that neutron capture therapy can beused to treat a large number of different cancers. BNCT has been foundto be effective and safe in the treatment of inoperable, locallyadvanced head and neck carcinomas that recur at sites that werepreviously irradiated with traditional gamma radiation. Thus, BNCT couldbe considered for a wider range of cancers. BNCT holds such promisebecause the dose to the cancer site can be greatly enhanced over thatproduced by γ-radiation sources. This is a consequence of the fact thatthe neutron-boron reaction produces the emission of short-range (5-9 umdistance) radiation, and consequently normal tissues can be spared. Inaddition, boron can achieve a high tumor-to-brain concentration ratio,as much as ten or more, thereby preferentially destroying abnormaltissue.

BNCT has been tested using either nuclear reactors or accelerators toproduce the neutrons, which are not practical or affordable for mostclinical settings. Reactors also do not produce an ideal neutronspectrum and are contaminated with γ-radiation.

Fusion generators produce fast neutrons from the deuterium-deuterium(DD) or the deuterium-tritium (DT) reactions and are, in general,smaller and less expensive than accelerators and reactors. Fast neutronsthus produced must be moderated or slowed down to thermal or epithermalneutron energies using, for example, water or other hydrogen bearingmaterials.

The fusion neutron generator has three basic components: an ion source,an electron shield and an acceleration structure with a target. The ionsare accelerated from the ion source to usually a titanium target using ahigh voltage potential of between 40 kV to 200 kV, which can be easilydelivered by a modern high voltage power supply. An electron shield isusually disposed between the ion source and the titanium target. Thisshield is voltage biased to repel electrons being generated when thepositive D+ ions that strike the titanium target. This prevents theseelectrons from striking the ion source and damaging it due to electronheating.

The target uses a deuterium D⁺ or tritium T⁺ absorbing material such astitanium, which readily absorbs the D⁺ or T⁺ ions, forming a titaniumhydride. Succeeding D⁺ or T⁺ ions strike these embedded ions and fuse,resulting in DD, DT or TT reactions and releasing fast neutrons.

Prior attempts at proposing fusion generators required the use of the DTreaction with the need for radioactive tritium and high accelerationpowers. High yields of fast neutrons/sec were needed to achieve enoughthermal neutrons for therapy in a reasonable length of time of therapytreatments. These prior schemes for achieving epithermal neutron fluxesare serial or planar in design: a single fast neutron generator isfollowed by a moderator, which is followed by the patient.Unfortunately, since the neutrons are entering from one side of thehead, the planar neutron irradiation system leads to a high surface orskin dosage and a decreasing neutron dose deeper into the brain. Thebrain is not irradiated uniformly, and cancer sites have lower thermalneutron dosage the further they are from the planar port.

A conventional planar neutron irradiation system 14 and its operation isshown in FIG. 1 labeled Prior Art. Conversion of fast neutrons 22 tothermal neutrons 30 takes place in a series of steps. First the fastneutrons 22 are produced by a cylindrical fast neutron generator 20 andthen enter a moderating means 18 where they suffer elastic scatterings(collisions with nuclei of the moderating material's atoms). This lowersthe fast neutrons to epithermal neutron 24 energies. A mixture ofepithermals 24 and thermal neutrons 30 are emitted out of a planar port16 and then enter the patient's head 26. The epithermal neutrons 24 aremoderated still further in the patient's brain and moderated further tothermal neutrons, finally being captured by the boron at the tumor site.The fission reaction occurs, and alpha and Li-7 ions are released,destroying the tumor cells.

The epithermal and thermal neutrons reach the patient's head through aplanar port 16 formed from neutron absorbing materials that form acollimating means 28. The thermal and epithermal neutrons strike thepatient's head on one side, and many neutrons escape or are not used.One escaping neutron 38 is shown as representative. This is aninefficient process requiring a large number of fast neutrons to beproduced in order to produce enough thermal neutrons for reasonabletherapy or treatment times (e.g. 30 min).

To achieve higher yields of fast neutrons the planar neutron irradiationsystem 14 requires that one use either the DD fusion reaction withextremely high acceleration powers (e.g. 0.5 to 1.5 Megawatts) or the DTreaction which has an approximate 100-fold increase in neutron yield forthe same acceleration power.

The use of tritium has a whole host of safety and maintenance problems.Tritium gas is radioactive and extremely difficult to eliminate once itgets on to a surface. In the art of producing fast neutrons thisrequires that the generator be sealed and have a means for achieving avacuum that is completely sealed. The generator head cannot be easilymaintained and usually its lifetime is limited to less than 2000 hours.This reduces the possible use of this generator for clinical operationsince the number of patients who could be treated would be small beforethe generator head would need replacement.

On the other hand, the use of the DD fusion reaction allows one skilledin the art to use an actively-pumped-vacuum means with roughing andturbo pumps. The generator can then be opened for repairs and itslifetime extended. This makes the DD fusion reaction neutron generatoroptimum for clinical use. The downside for the DD fusion reaction isthat high acceleration powers are required to achieve the desiredneutron yield required by prior art methods. Improving the efficiency ofproducing the right thermal neutron flux at the cancer site isimperative for achieving BNCT in a clinical and hospital setting.

SUMMARY OF THE INVENTION

In one embodiment a Boron neutron cancer treatment system is provided,comprising a secondary moderator having a central treatment chamber fora subject; and six substantially identical neutron generators, eachcomprising a pre-moderator block of moderating material having an uppersurface, a lower surface, a first and a second end, opposite sidesurfaces angled inward by thirty degrees along at least a portion of theheight, a first length, a first width substantially less than the firstlength, and a first thickness, a cylindrical acceleration chamber havinga first diameter substantially the first width of the pre-moderatorblock, sealed at one end to the upper surface of the pre-moderator blockadjacent the first end of the pre-moderator block, with a vertical axisperpendicular to the upper surface, the acceleration chamber having aheight and a top cover at a second end away from the pre-moderatorblock, a vacuum pump engaging the acceleration chamber at a right angleto the vertical axis, evacuating the acceleration chamber to amoderately high vacuum, a plasma ion chamber opening into theacceleration chamber through an ion extraction iris through the topcover of the acceleration chamber on the vertical axis of theacceleration chamber, a gas source providing deuterium gas to the plasmaion chamber, a microwave energy source ionizing the gas in the plasmaion chamber, a cylindrical primary isolation well extending asubstantial distance into the pre-moderator block from the uppersurface, centered on the vertical axis of the acceleration chamber, asecondary isolation well substantially in a shape of a hollow cylindersurrounding the primary isolation well, to a depth somewhat less thanthe substantial distance of the primary isolation well, within the firstdiameter of the acceleration chamber, a water-cooled titanium targetdisk having a target surface orthogonal to the axis of the accelerationchamber, the target disk having a diameter substantially smaller then adiameter of the isolation well, positioned at a lower extremity of theisolation well, the target disk biased to a substantial negative DCvoltage, and electrically grounded metal cladding covering all otherwiseexposed surfaces of the pre-moderator block. The six neutron generatorsare positioned around the secondary moderator with the axis of eachacceleration chamber passing through the center of the treatmentchamber, and with the angled sides of the neutron generators fullyadjacent.

In one embodiment the system further comprises six substantiallyrectangular spacing blocks of moderator material, one spacer blockplaced between each adjacent neutron generator with sides of the spacerblocks fully adjacent with the angled sides of the neutron generators.Also, in one embodiment the secondary moderator is shaped to fill allvolume between the neutron generators and the central treatment chamber.In one embodiment the secondary moderator is a block or blocks of solidmoderator material. In one embodiment the secondary moderator is acontainer filled with heavy water. And in one embodiment the secondarymoderator is a container filled with granulated moderator material.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

FIG. 1 (Prior Art) is a cross sectional view of a planar geometry forintroducing thermal neutrons into a patient's brain.

FIG. 2 is a cross sectional view of an embodiment of how multiple fastneutron generators are arranged around a hemispheric moderator tointroduce a uniform thermal neutron dose into a patient's head.

FIG. 3 is a perspective view of how multiple fast neutron generators areused in an embodiment of the invention to develop a high neutron doseinto a patient's head.

FIG. 4 is a cross sectional view of the arrangement of FIG. 3 with thepatient's head inside the interior of the neutron irradiation system.

FIG. 5 is a graph of the dose rate (Gy-equivalent/hr) as a function ofdistance from the surface of the head (skin) for the planar andhemispheric moderator (radial source) geometries.

FIG. 6 is a graph of the therapeutic ratio as a function of distancefrom the surface of the head (skin) for the hemispheric (radial source)and planar moderator geometries in an embodiment of the invention.

FIG. 7A is a cross sectional view of an embodiment of a cylindricalneutron irradiation system for the liver and other organs of the body.

FIG. 7B is a perspective view of the cylindrical neutron irradiationsystem for the liver and other organs of a body.

FIG. 8 is a cross sectional view of one of the embodiments of a neutronirradiation system wherein the neutron generators can be controlledindependently to maximize thermal neutron flux at the liver or otherorgan of a body.

FIG. 9 is a simplified view of the cross section of the irradiationsystem that uses neutron generators that can be controlled independentlyof one another.

FIG. 10 is a graph of the therapeutic ratio as a function of distancealong the axis of the liver in cm.

FIG. 11 is a graph of the dose rate as a function of distance along theaxis of the liver in cm.

FIG. 12A is a perspective view of a modular neutron generator in anembodiment of the invention.

FIG. 12 B is a perspective cross-section view of the module of FIG. 12Ataken along an axis of the acceleration chamber, at a right angle to anaxis of the turbo vacuum pump.

FIG. 12 C is a perspective cross-section view of the module of FIG. 12Ataken along an axis of the turbo vacuum pump.

FIG. 13 A is a planar view of six modular generators arrayed around amoderator and chamber for a patient, in an embodiment of the invention.

FIG. 13 B is a perspective view of the system of FIG. 13 using sixmodular neutron generators in an embodiment of the invention.

FIG. 13 C is a perspective view of a cylindrical neutron irradiationsystem using eight modular generators with one removed to show how anirradiation system is assembled in an embodiment of the invention.

FIG. 13 D is a planar diagram of modular generators with a fluidmoderator and arrayed to maximize dose to a cancer site in a brain, inan embodiment of the invention.

FIG. 14 A is a simplified, mostly diagrammatical view of a centralcylinder with a human head (phantom) inside a helmet moderator andneutron reflector with eight modular neutron generators in an embodimentof the invention.

FIG. 14B is a simplified, mostly diagrammatical section view taken alongsection line 14B-14B of FIG. 14A.

FIG. 15 is a graph showing an expected horizontal dose equivalent rate(Sv/hr) as a function of horizontal position across a phantom (head) inan embodiment of the invention.

FIG. 16A is a perspective view of a module for a small animal neutronradiation system employing four modules.

FIG. 16B is a simplified top plan view of the small animal neutronirradiation system of FIG. 16A.

FIG. 16C is a simplified cross section of the small animal neutronirradiation system of FIG. 16A.

FIG. 16D is an exploded plan view of the small animal neutronirradiation system of FIG. 16A.

DETAILED DESCRIPTION

In the following descriptions reference is made to the accompanyingdrawings that form a part hereof, and in which are shown by way ofillustration specific embodiments in which the invention may bepracticed. It is to be understood that other embodiments may beutilized, and structural changes may be made without departing from thescope of the present invention.

Uniform Delivery of Thermal Neutrons to the Cancer Sites

To achieve extremely high thermal neutron fluxes uniformly distributedacross a patient's head, for example, a hemispherical geometry is usedin one embodiment of the invention. This unique geometry arranges fastneutron sources in a circle around a moderator whose radial thickness isoptimized to deliver a maximum thermal neutron flux to a patient'sbrain. This embodiment produces a uniform thermal neutron dose within afactor of 1/20^(th) of the required fast neutron yield and line-voltageinput power of a conventional planar neutron irradiation system. Thisarrangement permits using a relatively safe deuterium-deuterium (DD)fusion reaction (no radioactive tritium) and commercial high voltagepower supplies operating at modest powers (50 to 100 kW).

FIG. 2 is a cross sectional view of a hemispheric neutron irradiationsystem 36 according to one embodiment of the invention. Multiple fastneutron generators 68 surround a hemispheric moderator 34, which in turnsurrounds the patient's head 26. Titanium targets 52 are distributedaround the perimeter of the hemispheric moderator 34. Surrounding themoderator 34 and the fast neutron generators 68 is a fast-neutronreflector 44.

In the moderator 34, moderating material such as ⁷LiF, high densitypolyethylene (HDPE), and heavy water are shaped in a hemisphere that isshaped around the head of the patient. The optimum thickness of thehemispheric moderator for irradiation purposes is dependent upon thematerial's nuclear structure and density.

FIG. 3 shows a perspective view of a patient 58 on a table 54 with thepatient's head inserted into hemispheric irradiation system 36. Thepatient 58 lies on the table 54 with his head inserted into hemisphericmoderator 34. Surrounding the moderator is neutron reflecting material44, such as lead or bismuth.

Referring again to FIG. 2, fast neutrons 22 are produced by fast neutrongenerators 68. Generators 68 are composed of titanium targets 52 and ionsources 50. Ion beams are produced by ion sources 50 and acceleratedtoward titanium targets 52 which are embedded in hemispheric moderator34. A DD fusion reaction occurs at the target, producing 2.5 MeV fastneutrons 22.

The fast neutrons 22 enter the moderator 34 wherein they are elasticallyscattered by collisions with the moderator atom's nuclei. This slowsthem down after a few collisions to epithermal neutrons 24 energies.These epithermal neutrons 24 enter the patient's head 26 wherein theyare moderated further to thermal neutron 30 energies. These thermalneutrons 30 are then captured by boron-10 nuclei at the cancer site,resulting in a fusion event and the death of proximal cancer cells.

Fast neutrons 22 are emitted isotropically from titanium target 52 inall directions. Outwardly traveling fast neutrons 42 are reflected back(reflected neutron 48) by fast neutron reflector 44, while inwardlytraveling fast neutrons 40 are moderated to epithermal energies andenter the patient's head 26, where further moderation of the neutrons tothermal energies occurs.

A shell of protective shielding 56 is also shown in FIG. 2. In someembodiments, this may be necessary for shielding both the patient andthe operator from excessive irradiation due to neutrons, x-rays andgamma radiation. The shielding can be made of a variety of materialsdepending upon the radiation components one wishes to suppress.

In some embodiments, fast neutron reflector 44 is made of lead orbismuth. The fast neutron reflector also acts as a shielding means toreduce emitted gamma rays and neutrons from the hemispherical neutronirradiation system 36. As one skilled in the art will realize,gamma-absorbing or other neutron reflector means can be placed in layersaround the hemispherical neutron irradiation system 36 to reducespurious and dangerous radiation from reaching the patient 58 and theoperator.

Hemispheric moderator 34, fast neutron reflector 44 and head 26 acttogether to concentrate the thermal neutrons in the patient's head. Thepatient's head and the moderator 34 act in concert as a singlemoderator. With a careful selection of moderating materials andgeometry, a uniform dose of thermal neutrons can be achieved across thepatient's head and, if a boron drug is administered, a large and uniformtherapeutic ratio can be achieved.

The invention gives a uniform dose of thermal neutrons to the head whileminimizing the fast neutron and gamma contributions. The requiredquantity of fast neutrons to initiate this performance is reducedcompared to that of prior art planar neutron irradiation systems (seeFIG. 1).

A cross section perspective view of the hemispheric neutron irradiationsystem 36 in an embodiment of the invention is shown in FIG. 4. Thiscross-section view is of a radial cut directly through the patient'shead 26 and hemispherical neutron irradiation system 36. As shown inthis embodiment, ten fast-neutron generators 68 composed of ion sources50 with titanium targets 52 are radially surrounding the hemisphericmoderator 34 and the patient's head 26. The titanium target 52 in thisembodiment is a continuous belt of titanium surrounding the moderator34. The titanium targets can also be segmented, as was shown in FIG. 2.The ion sources in this embodiment are embedded in fast neutronreflector 44.

There are a number of materials one could select for the moderator 34 toachieve maximum thermal neutron flux at the patient's head 26. Theperformance of HDPE, heavy water (D₂O), graphite, ⁷LiF, and AlF₃ wasanalyzed using the Monte Carlo Neutral Particle (MCNP) simulation. Ingeneral, there is an optimum thickness for each moderator material thatgenerates the maximum thermal flux at the patient's head (or other bodypart or organ). The thermal neutrons/(cm²-s) was calculated for thesematerials as a function of moderator thickness d₃, where d₄=25 cm, andfast neutron reflector 44 is d₁=50 cm thick and is made of lead. As inall our calculations, the combined fast neutron yield striking the areafrom all the fast neutron generators 68 is assumed in the MCNP to be10¹¹ n/s. The optimum thickness, range of thicknesses and maximumthermal neutron flux (E<0.5 eV) are given in Table I for variousmoderator materials. These are approximate values given to helpdetermine the general dimensions of the moderator.

TABLE I Moderator Thickness Optimum Range of Moderator Thicknessthickness Maximum Flux Material d₃ (cm) d₃ (cm) (n/cm²-sec) HDPE 6  4-107 × 10⁸ D₂O 15  9-25 2 × 10⁸ Graphite 20 19-20 9 × 10⁷ ⁷LiF 25 20-30 3 ×10⁷ AlF₃ 30 20-40 1.5 × 10⁷  

The calculation of the therapeutic ratio is also important and dependsupon the organ in question (brain, liver) and the body mass of thepatient. Although HDPE gives the highest flux, it gives a lowertherapeutic ratio compared to ⁷LiF. The designer is expected to docalculations similar to this to determine the optimum geometry for theneutron irradiation system.

The MCNP simulation was used to determine the delivered dose andtherapeutic ratio to the patient 58 and compare it to a planar neutronirradiation system. In one simulation, moderator 34 is composed of 7LiFwhose thickness is d₃=25 cm. The inner diameter of the moderator (holefor head) is d₄=25 cm. The spacing between hemispheric fast neutronreflector 44 and hemispheric moderator 34 is d₂=10 cm. The head isassumed to be 28 cm by 34 cm. Fast neutron reflector 44 is made of d₁=20cm thick lead in one embodiment. Thicker values of d₁ increase the tumordose rate. At a thickness of 10 cm, the tumor dose rate is aboutone-half the value at a thickness of 50 cm. Fast neutron generators 68are assumed to emit a total yield of 10¹¹ n/sec. The combined titaniumtargets 52 give a total neutron emission area of 1401 cm².

In the MCNP simulation BPA (Boronophenylalanine) was used as a deliverydrug. The concentration of boron in the tumor was 68.3 μg/gm and in thehealthy tissue was 19 μg/gm. The calculated neutron dose rates inGy-equivalent/hr are plotted in FIG. 5 as a function of distance fromthe skin to the center of the head. The calculated dose rates arecomparable to those used for gamma radiotherapy, typically 1.8 to 2.0 Gyper session. For the same dosage, at a rate of 3 Gy-equivalent/hr, thesession length would be from 30 to 40 min. long. These session times areconsidered reasonable for a patient to undergo.

For this simulation, the therapeutic ratio for the hemispherical neutronirradiation system is plotted in FIG. 6 as a function of distance fromthe skin to the center of the skull. The therapeutic ratio is defined asthe delivered tumor dose divided by the maximum dose to healthy tissue.A therapeutic ratio of greater than 3 is considered adequate for cancertherapy.

The conventional planar neutron irradiation system requires largerfast-neutron yields (10¹² to 10¹³ n/s) to achieve equivalent dose ratesand therapeutic ratios. In FIG. 5, a planar neutron irradiation system14 of FIG. 1 is compared with that of a hemispheric neutron irradiationsystem 36 (FIGS. 2, 3, 4) in one embodiment of the present invention,using the same source of fast neutrons (10¹¹ n/s). As can be seen fromFIG. 5, the hemispherical neutron irradiation system (called radialsource in FIG. 5) achieves a dose rate of about a factor of 20 over thatof the conventional planar neutron irradiation system 14. The planargeometry needs a fast neutron source of 2×10¹² n/s to achieve the sameresults. Indeed, if a DD fusion generator is used, then the planarsource requires a factor of 20× increase in wall-plug power or 2.0 MW, aprohibitively large power requirement.

In addition, as can be seen from FIG. 5, over a ±5 cm distance acrossthe head center, hemispheric neutron irradiation system 36 has less thana 10% variation in dosage. A uniform dose rate is crucial for thetreatment of GBM, where we want to maintain a maximum therapeutic ratioand tumors may have distributed themselves across the brain.

Hemispherical neutron radiation system 36 in embodiments of theinvention also gives a more uniform therapeutic ratio (FIG. 6) acrossthe brain. The ratio is more uniform for the radial source and requiresonly 1/20^(th) of the fast neutron yield of the planar source (FIG. 1).

Other materials can be used for hemispheric moderator 34 in alternativeembodiments. As those skilled in the art will know, high densitypolyethylene (HDPE), heavy water (D₂O), Graphite and ⁷LiF can also beused. In addition, combinations of materials (e.g. 40% Al and 60% AlF₃)can also be used. Different thicknesses d₁ of moderator can be used tooptimize the neutron flux and give the highest therapeutic ratio.

The term “neutron generator or source” is intended to cover a wide rangeof devices for the generation of neutrons. The least expensive and mostcompact generator is the “fusion neutron generator” that producesneutrons by fusing isotopes of hydrogen (e.g. tritium and deuterium) byaccelerating them together using modest acceleration energies. Thesefusion neutron generators are compact and relatively inexpensivecompared to linear accelerators that can produce directed neutron beams.

Other embodiments depend upon the selection of the plasma ion sourcethat is used to generate the neutrons at the cylindrical target. Theseare (1) the RF-driven plasma ion source using a loop RF antenna, (2) themicrowave-driven electron cyclotron resonance (ECR) plasma ion source,(3) the RF-driven spiral antenna plasma ion source, (4) the multi-cuspplasma ion source and (5) the Penning diode plasma ion source. Allplasma ion sources can be used to create deuterium or tritium ions forfast neutron generation.

Cylindrical Irradiation System for the Liver and Other Cancer Sites.

FIGS. 7A and 7B shows another embodiment of the invention which uses acylindrical geometry to irradiate other organs and parts of patient 58,such as the liver 76. FIG. 7A is a cross sectional view of cylindricalneutron irradiation system 62 and FIG. 7B is a perspective view of thesame embodiment. In this embodiment eight fast-neutron generators 68surround a cylindrical moderator 46. These generators 68 all emit theirfast neutrons at the surface of the moderator. A cylindrical fastneutron reflector 44 surrounds the cylindrical moderator 46.

As in the case of the hemispheric moderator 34, the cylindricalmoderator 62 can be composed of well-known moderating materials such as⁷LiF, high density polyethylene (HDPE), and heavy water. These areshaped in a cylinder that surrounds the patient. The optimum thicknessof the cylinder moderator for neutron capture purposes is dependent uponthe material nuclear structure and density.

In this embodiment, fusion neutron generators are used to supply thefast neutrons. Fast neutron generator 68 is composed of a titaniumtarget 52 and an ion source 50 as before. The titanium targets arecontiguous to the cylindrical moderator 46. Ion beams 60 are acceleratedusing a DC high voltage (e.g. 100 kV) to the titanium target 52 wherefast neutrons are produced from the DD fusion reaction. The fastneutrons are emitted isotropically from the titanium targets 52 on themoderator, some moving out to the fast neutron reflector 44 and othersinwardly to be moderated immediately to epithermal or thermal energies.Those reflected come back into the cylindrical moderator 46 where theyare moderated to epithermal and thermal energies, making their wayfinally to the patient 58.

Cylindrical neutron irradiation system 62 permits uniform illuminationof a section of the patient's body (e.g. liver) as compared to theconventional planar neutron irradiation system. In the case of thebrain, the body itself acts as part of the moderation process,thermalizing epithermal neutrons coming in from cylindrical moderator46.

As one skilled in the art will realize, other cancers, such as throatand neck tumors, can be effectively irradiated by a hemisphericalneutron irradiation system such as system 36. The thickness and materialcontent of the moderator can be adjusted to maximize the desired energyof the neutrons that enter the patient. For example, for throat and necktumors, the moderator can be made of deuterated polyethylene or heavywater (D₂O) to maximize thermal neutron irradiation of the tumor nearthe surface of the body. For deeper penetration of the neutrons onemight make the moderator out of AlF₃, producing epithermal neutrons.These would be optimum for reaching the liver and producing uniformillumination of that organ.

Segmented Moderator

In yet another embodiment, fast neutron sources with segmentedmoderators may be individually moved to achieve a uniform dose acrossthe liver or other cancer site. This geometry produces a uniform thermalneutron dose with a factor of between 1/10^(th) and 1/20^(th) of therequired fast neutron yield and line-voltage input power of previouslinear designs. This again permits the use of the relatively safedeuterium-deuterium (DD) fusion reaction (no radioactive tritium) andoff-the-shelf high voltage power supplies operating at modest power(≤100 kW).

A segmented neutron irradiation system 70 in an embodiment of theinvention is shown in FIG. 8. Ten fast neutron generators 68, each witha wedge-shaped moderator 74, surround the patient 58. The exact shape ofeach moderator can vary and can be of other geometries. Each generatorand moderator pair can be moved independently of the others to achieveuniformity of the neutron flux across the liver, organ, or body part.

In between the wedge-shaped moderators 74 more moderating material(“filler moderating material” 72) is inserted, forming a large singlemoderator. The “filler” moderating material 72 can be heavy water orpowered moderating materials such as AlF₃. Pie shaped fillers ofmoderating material can also be fitted into the spaces between thewedge-shaped moderator 74. Since neutrons scatter easily, there can besome space between the wedge-shaped moderators 74 and the pie shapedfillers without undue loss of neutron moderating efficiency.

The neutron yield from and the position of each fast neutron generator68 can be adjusted to achieve uniformity across the liver or body part.The position and the neutron yield of the generator can be varied toachieve the desired radiation dose at a particular location in thepatient's body. Since the cancer can be located in any part of the body,this benefit can be particularly useful for optimizing the dose at thecancer site.

Surrounding the entire fast neutron/moderator system is a cylindricalfast neutron reflector 44. Fast neutrons are produced by the fastneutron generators 68 and enter the moderators 74 where they areelastically scattered by collisions with the moderator atoms' nuclei,slowing them down after a few collisions to epithermal energies. As inthe other embodiments, these epithermal neutrons enter the patient 58and liver 76, wherein they are moderated further to thermal neutronenergies.

The invention in various embodiments provides a uniform dose of thermalneutrons to the liver, organ or body part while minimizing fast neutronand gamma contributions. The required number of fast neutrons (e.g.2×10¹¹ n/s) to initiate this performance is again reduced compared tothat (e.g. 2×10¹³ n/s) needed for the planar neutron irradiation systemof the prior art.

Another embodiment of the segmented design is shown in FIG. 9. The shapeof the neutron irradiation system 78 is elliptical, with six sources offast neutrons shown as distributed targets embedded in the insideelliptical moderator 96. Fast neutrons 22 are emitted isotropically inall directions. Those fast neutrons 22 moving outwardly are reflectedback (see arrow 48) by fast neutron reflector 44, while fast neutronstraveling inwardly 22 are moderated to epithermal energies and enter theliver 76, where further moderation of the neutrons to thermal energiesoccurs. The inside elliptical moderator 96, outside elliptical moderator98, reflector 44 and patient's body 58 act together to moderate andconcentrate the thermal neutrons into the patient's liver 76. With acareful positioning of the moderators and fast neutron sources 90, 92,94, a uniform dose can be achieved across the patient's liver, and, witha boron drug administered to the tumor, an excellent therapeutic ratiocan be achieved.

Elliptical neutron irradiation system 78 in FIG. 9 is a simplifiedcross-sectional view of the patient 58 inside the elliptical moderator96. This cross-section view is of a radial cut directly through thepatient's torso and the moderator and fast neutron generator system. Tomaintain visual simplicity, only the titanium targets are shown and notthe ion sources. Thus, six fast-neutron sources are represented by threeflat titanium targets 90, 92, 94. The rest of the fast neutron generatoris not shown. Other components (e.g. plasma ion source) are neglected inthe analysis. The wedge-shaped moderators 74 (used in FIG. 8) are alsonot shown in FIG. 9.

For a simple simulation of the neutron irradiation system, the targets90, 92, 94 are the sources of the fast neutrons and are arranged in anelliptical material 96 (e.g. AlF₃, LiF). The effect of the moderatingmaterial 96, the fast neutron reflector 44 and the patient's body 58were calculated using a Monte Carlo N-particle (MCNP5) transport code todetermine how fast the neutrons were converted to thermal neutrons inthe neutron irradiation system.

Dosage calculations were made along a central axis of the liver. Thefast neutron sources (titanium targets) are 2 cm×2 cm in area, eachproducing 10¹¹/N n/s, where N is the number of sources. The human body58 dimensions are 35.5 cm along the major axis and 22.9 cm along theminor axis. The inner elliptical moderator 96 is made of ⁷LiF and 10 cmthick, while the outer moderator 98 is made of AlF₃ and 40 cm thick. Thefast neutron reflector 44 is made of lead 50 cm thick. Boron-10concentration is 19.0 μg/g in the healthy tissue and 68.3 μg/g in thetumor. The six sources are located in cms at: (−15,18.06,0)(−15,−18.06,0) (−17,17,0) (−17,−17,0) (0,15.85,0) (0,−15.85,0). Thesemeasurements are made along the axis of the liver 76 from the point(−15,0,0) to (−5,0,0). In the x-direction, the first two sources 90 arecentered about the left edge of the liver shown in FIG. 9, the twosources 92 are centered about the edge of the body, and the third two 94are located above and below the origin. The origin is shown in FIG. 9 asa small cross + at the center of the body in the plane of the liver.

FIG. 10 shows the therapeutic ratio for a large single dose, and thetherapeutic ratio for multiple small doses (where the photon dose tohealthy tissue is not included) plotted as a function of distance alongthe axis of the liver. The photon dose can be neglected if there is someamount of time between doses. Many of the body's healthy cells canself-repair and recover between doses. The expected therapeutic ratio isbetween these two curves when there is fractionation into multipledoses. In this simulation, BPA was again used as the delivery drug withthe concentration of boron in the tumor at 68.3 μg/gm and in the healthytissue at 19 μg/gm.

FIG. 11 indicates that the goal of having an extremely uniform dosage tothe tumor has been achieved, with about ±6% variation along thex-dimension. The calculated dose rates are comparable to those used forgamma radiotherapy, typically 1.8 to 2.0 Gy-equivalent per hour if weincrease the total neutron yield to 2×10¹¹ to 3×10¹¹ n/s. Thus, atapproximately 2×10¹¹ to 3×10¹¹n/s it is possible to obtain a therapeuticratio and uniform dosage to a tumor. Approximately 10 to 20 treatmentsof 30 to 40 minutes would be required, with a good therapeutic ratio,uniformity of dosage, and the opportunity for healthy tissue repairbetween treatments.

Once again, the planar neutron irradiation systems require high fastneutron yields to drive them. In one prior art system known to theinventors a fast neutron source of 3×10¹³ n/s is needed to obtainrealistic treatment time of ˜1-2 hours. Using a D-T neutron source witha yield 10¹⁴ n/s, acceptable treatment times were obtained (30 to 72minutes with single beam and 63 to 128 minutes with 3 beams of differentdirection). But these are impossible yields to achieve with realisticwall plug powers. Instead of 50 to 100 kW for the hemispheric andcylindrical neutron irradiation systems, it would take a minimum of 0.5MW to achieve adequate yield for the planar geometry with a DTgenerator. These are high powers for clinics and hospitals.

As one skilled in the art knows, other cancers, such as throat and necktumors, can be effectively irradiated by the neutron irradiation system.The thickness and material content of the moderator can be adjusted tomaximize the desired energy of the neutrons that enter the patient. Forexample, for throat and neck tumors, the moderator can be made ofdeuterated polyethylene or heavy water (D₂O) to maximize thermal neutronirradiation of the tumor near the surface of the body. For deeperpenetration of the neutrons one might make the moderator out of AlF₃,producing epithermal neutrons. These would be optimum for reaching theliver and producing uniform illumination of that organ.

Modular Generators

INTRODUCTION

As is shown in FIGS. 8 and 9, multiple modular generators may be encasedin moderator material and may be arrayed to maximize thermal neutronflux at a cancer tumor location. Fast 2.5 MeV neutrons must be slowed(moderated) to energies (usually epithermal) that will penetrate to thecancer site without too many neutrons being lost in their travel to thecancer via capture by healthy tissue. These modular generators act asindependent neutron sources and each may be optimized by adjustment ofeach individual beam's energy, direction and intensity. The modulargenerators can be arranged to fit a site in a particular subject'scomponent location and structure. This is true also for cancer tumorlocation.

The energy of the neutrons can also be adjusted by adding or subtractingmoderator material. This can be done more easily than with a single beamLINAC or reactor, which usually has a fixed beamline that is integral tothe neutron source. In the prior art some adjustment can be made, butthe DD fusion generator in embodiments of the invention, being muchsmaller, can have more degrees of freedom in direction, intensity andmoderation. This has an added benefit of aiding physicians in tailoringneutron radiation to the patient's cancer.

Comparison to Linear Accelerators and Reactors.

Modular generators in various embodiments of the present invention mayalso form and be part of the mechanical structure of a cancerirradiation system. This has an added benefit of moving the neutronsources as close as possible to the cancer site and the diseased bodypart, resulting in efficient use of the neutron source. The neutrons arebeing emitted in a 4π solid angle from the modular generators, so thecloser to cancer site, the more of the fast neutron flux is beingutilized. Linear accelerators (LINACs), which are somewhat collimated,are further from the cancer site and cannot provide this advantage.

Compared to a linear accelerator, which can be several meters long orlonger and may include large microwave power sources, the DD fusionsources in embodiments of the invention are less than one meter long andcomprise compact microwave sources that can either be solid statemicrowave sources or small, inexpensive, single microwave ovenmagnetrons. The accelerator structure in embodiments of the invention iscompact and includes a pre-moderator 118 that adds only from 5-10 cm ofHigh-Density Polyethylene (HDPE) or 15-20 cm of polytetrafluoroethene(PTFE) Teflon to produce a first stage of neutron beam tailoring. Thepre-moderator in these embodiments is an integral part of each modulargenerator, as is taught below with reference to several figures. Inalternative embodiments other pre-moderator materials can be used suchas AlF₃, MgF₂, ⁷LiF, and Fluental (trade name).

Smaller, Nontoxic, Less Complex Targets for Neutron Production

The modular DD fusion generator 118 in embodiments of the presentinvention uses a small titanium target (e.g. a 5 cm diameter disk oftitanium backed by water-cooled copper fins) to produce neutrons. Thetarget is supported directly on the pre-moderator, which is an integralpart of the apparatus in this application, termed a modular generator.Linacs and other methods in the conventional arts use larger or toxictargets that require complex cooling and rotation. For example, theneutron source used by Neutron Therapeutics has a 2.6 MeV electrostaticproton accelerator and a rotating, solid lithium target for generatingneutrons. In that prior-art process the Lithium becomes radioactive andtoxic, and when exposed to air, it disintegrates. This prior art sourcehas a large target chamber housing a large Li disk which is rotated in apowerful 2.8 MeV proton beam produced by a large accelerator. TheLithium wheel is roughly 2 meters in diameter and has been divided intopie-shaped sections that are removed by mechanical robotic means. Inembodiments of the present invention, the Ti target is a relativelysmall diameter (˜5 cm) and is typically attached with 6-8 screws to thepre-moderator block and is sealed to the block with a Viton “O” ring.The Ti targets in embodiments of the invention can be easily manuallyremoved and replaced. They also have a long lifetime and have beentested for over 4000 hours with no failures.

Nuclear reactors are large structures with a substantial amount ofshielding (water and concrete) and cooling systems to maintain the hotreactor core. Reactors provide primarily thermal neutrons that must beraised up in energy using an energy multiplier, and then the neutronbeam must be improved to IAEA standards to produce epithermal neutronswith minimal gamma radiation.

Optimizing Neutron Energy for Penetration and Minimum Damage to HealthyTissue

For tumors at depths in a subject of 3 cm or more, a goal for themoderator is to provide a neutron beam that has its energy clusteredabout 10 keV at the skin, in order to provide sufficient energy topenetrate a minimum of several centimeters into a human target whileavoiding higher energies that are more damaging to human tissue. Highconversion to epithermal energies occurs in HDPE at a thickness ofapproximately 5 cm, but it also produces a high yield of thermalneutrons and 2.2 MeV gammas that can damage the healthy tissue at theskin.

Modular Generators

In embodiments of the present invention modular generators are veryimportant components. The modular generator combines multiple functionsthat were separate functions in the prior art. These integratedfunctions include both neutron production and beam tailoring. FIG. 12Ais a perspective view of an individual modular generator 118 in anembodiment of the invention.

FIG. 12B is a cross section of the modular generator 118 of FIG. 12Ataken along an axis of an acceleration chamber 100 for ion beamgeneration and containment, and at a right angle to the axis of a turbovacuum pump 124 that is part of the modular generator 118. FIG. 12C is across section of the modular generator 118 of FIG. 12A taken along theaxis of the acceleration chamber 100, and along the axis of the turbovacuum pump 124, at a right angle to the section of FIG. 12B. Eachmodular generator 118 can operate independently of the other modulargenerators and each possesses all required components to generateneutrons. Further, the various modular generators may havepre-moderators shaped to engage other building blocks of a project, suchas adjacent generators or spacing moderators, as is described inenabling detail below.

Viewed as in FIGS. 12A, B and C, each modular generator 118 comprises apre-moderator 108 that is made of material known to moderate energy ofenergetic neutrons. In most embodiments the pre-moderator is a solidblock of material, with a rather complicated shape for certain purposes.Modular generator 118 has three key elements: (1) a deuterium ion source102, (2) an acceleration chamber 100, through which deuterium ions maybe accelerated, and (3) a titanium target 106 (shown in FIGS. 12B and12C) that is bombarded by the deuterium ions to produce high-energyneutrons. The deuterium ion source 102 has an attached microwave source160, and microwave slug tuners 172, connected by a cable 178. Deuteriumgas is leaked slowly into a plasma ion chamber 174 at the upper end ofthe acceleration chamber, where microwave energy ionizes the gas,creating deuterium D+ ions.

The gas is ionized by microwave energy, and Deuterium (D+) ions arecreated and accelerated out through an ion extraction iris 138 intoacceleration chamber 100, and through an electron suppression shroud 180which deflects back-streaming electrons from being accelerated back intothe plasma source, which could damage the apparatus. Electrons are beingcreated by collisions of the D+ ions in the deuterium gas that are beingcreated in the acceleration chamber.

The deuterium ions are positively charged, and target 106 is negativelycharged to a level of from 120 kV to 220 kV, and the D+ ions arestrongly attracted to negatively biased target 106. Acceleration chamber100 is connected to a turbo vacuum pump 124 that provides a modestvacuum in one embodiment of about 10⁻⁶ Torr, minimizing scattering ofthe D⁺ ions as they travel from the extraction iris 138 to the target106. Titanium target 106 is positioned in a primary electricallyinsulating well 181 at the bottom of the chamber embedded into thepre-moderator material, which may be UHMW, HDPE or Teflon, of thepre-moderator 108. There is further a secondary electrical insulatingwell 182 surrounding the primary electrical insulating well. The surfaceof the moderator material in the primary and secondary electricalinsulating wells may be seen as a corrugated insulator causing anysurface charge to follow a curved path taken in any direction. Thepurpose is to provide a very long surface path to prevent electrons fromtraveling from the target to acceleration chamber 100 wall or anygrounded element, and to avoid surface electrical breakdown or flashoverin that surface path. As those skilled in the art know, the wells forman electrical insulating path. Additional corrugations or wells can beadded to lengthen the path.

Pre-moderator 108 has a high voltage bus bar 122 and fluid coolingchannels 120 to and from the target. The high voltage is introduced viaa high voltage receptacle 130 which is connected to the high voltage busbar. Pre-moderator 108 acts as a HV insulator and as a mechanicalsupport for the target 106 at a high negative bias. The pre-moderator108 has metal cladding 140 at ground potential to minimize high voltagebreakdown through the pre-moderator plastics. When in operation the D⁺ions in the ion beam are attracted to the titanium target 106, wherefast (2.5 MeV) neutrons are produced in a resulting DD fusion reaction.

FIG. 13A illustrates an assembly of six modular generators 118, whereinpre-moderators 108 are spaced apart by spacers 128 which are also madeof moderator material. FIG. 13B shows the arrangement of FIG. 13A inperspective. FIG. 13C shows the arrangement of FIG. 13B with one modulargenerator 118 removed from the assembly. FIG. 13D is a more diagrammaticillustration showing an arrangement in which modular generators may bemounted on translation and rotation mechanisms to be positioned tomaximum irradiation of a cancer site. As is shown in FIGS. 13A-D themodular generators in embodiments of the invention may be arranged in anarray to form a complete and moveable system of irradiating neutronsources with pre-moderators. For example, as shown in FIG. 13A-C, in thesimplest configuration of the array, the modular generators may form acircle around a human torso or body part. The modular generators can bemoved into three dimensional arrays around the subject to maximizeneutron flux to a cancer site 148 that may not be centered on a bodypart 146, illustrated as a human brain in FIG. 13D. Thus, depending uponbody contour, shape and size, and cancer location and distribution, themodular generators may be moved to adapt to the shape and tumor locationin order to maximize the dose to the cancer and to minimize the dose tothe other body parts. Referring to FIG. 13D, rotation 150 andtranslation 151 of the modular generator 118 can be achieved withelectrical motors attached to the modular generator 118.

Seven Functions of the Pre-Moderator

Because the titanium target is on the pre-moderator (first stage ofmoderation), fast neutrons coming from the target immediately enter thepre-moderator and quickly moderated to thermal or epithermal energies.The pre-moderator also provides mechanical support, high voltage supplyand cooling fluid transport to the titanium target. Exemplarypre-moderator materials that may accomplish this are Teflon and HDPE.Both Teflon and HDPE are excellent high voltage dielectrics which canalso support a HV bus bar 122 and water channels 120 to be used totransport HV and the cooling fluids to the Ti target, as shown in FIG.12C. As shown in FIGS. 12A, B, C a single generator 118 consists of anacceleration chamber 100, an ion source 102 emitting deuterium ions, atitanium target 106 and a pre-moderator 108. Pre-moderator 108 alsoprovides a function of being a high voltage insulator for high voltagebus bar 122 that delivers high voltage (e.g. 80 kV to 300 kV)) totitanium target 106, and a water channels 120 that deliver cooling fluidto the titanium target 106. The high voltage is delivered from a highvoltage power supply through a standard HV receptacle 130 to the bus bar122 and then on to the titanium target 106, all of which are mounted inthe pre-moderator 108.

In various embodiments of the invention the pre-moderator 108 performsseven functions: (1) moderation, (2) mechanical support of the titaniumtarget, (3) cooling fluid transport to the target, (4) high voltagetransport to the target, (5) minimum surface flashover, (6) and aportion of a high vacuum container (a wall) with no out gassing (7).These seven attributes permit a substantial reduction of distance andamount of material between the fast neutron source and the patient, thushelping to maintain a maximum neutron flux delivered to the patient.

Modular Generators Around a Subject

FIGS. 13A-D show how the generators may be arranged. In FIG. 13A, sixmodular generators 118 form a ring around a secondary moderator 112 andare part of a structure formed by secondary moderator 112, spacers 128,and pre-moderators 108. Pre-moderators 108 and secondary moderator 112provide the moderation function by slowing the neutrons down toepithermal energies (function #1). These elements also form a mechanicalsupport (function #2) for the entire generator and moderator system.

Secondary moderator 112 may also be a separate section attached directlyto the modular generator just after the pre-moderator, each separatefrom the other instead of being in a ring 112 as in FIG. 13A.

As shown in FIG. 12B-C, fluid transport (function #3) is suppliedthrough channels 120, which delivers cooling fluid to target 106 tomaintain the target at an acceptable operating temperature. Eachgenerator is supplied with a separate cooling fluid input and output,wherein cooling fluid is provided through a connector 132 shown in FIGS.12A-12C. Thus, the pre-moderator supplies fluid transport (function #4).High voltage is delivered via high voltage bus 122, which passes throughpre-moderator 108 (function 4, high voltage transport). HDPE, UHMW andTeflon are excellent insulators and withstand high voltage flashover(function #6). All three may be used in vacuum systems without excessiveout gassing and may help maintain the system vacuum (function #7). Theachievement of these seven functions provides a very compact andflexible neutron source.

The Secondary Moderator

Secondary moderator 112 (FIGS. 13A-C) may comprise any one of or acombination of multiple moderator materials that optimize both themaximum flux and neutron energy for maximum dose to the cancer site.Selection (material, size and shape) may be varied depending on depth ofthe cancer in the subject and a desired dose at the cancer site. Thesecondary moderator may be D₂O (heavy water) for delivery of thermalneutrons to, for example, throat and neck cancers, or a combination ofAlF₃ and Teflon for delivery of epithermal neutrons to brain tumors. Therecommended levels of fast, thermal and gamma emission by IAEA are givenin Table I.

TABLE 1 IAEA Recommended values in the beam exit window. IAEARecommended BNCT beam port parameters value ϕ_(epithermal) (n cm⁻² s⁻¹) ~10⁹ ϕ_(epithermal)/ϕ_(fast)  >20 ϕ_(epithermal)/ϕ_(thermal) >100D_(fast)/ϕ_(epithermal) (Gy cm²) <2 × 10⁻¹³ D_(γ)/ϕ_(epithermal) (Gycm²) <2 × 10⁻¹³ Fast energy group (ϕ_(fast)) E >10 keV Epithermal energygroup 1 eV ≤ E ≤ 10 Thermal energy group (ϕ_(thermal)) E <1 eV

These IAEA recommended values depend upon older drugs, such asp-Boronophenylalanine (BPA) that have been approved for use in humans bythe Food & Drug Administration (FDA) for other medical applications.Delivery of higher boron concentrations to a cancer site may depend tosome extent on newer drugs to be developed, and may permit lower power,less efficient neutron beams to be used. Since treatment time might alsobe faster, the neutron beam quality need not be as high. DD fusiongenerators in embodiments of this invention have relatively low beamflux, thus permitting them to be used for cancer therapy.

In some embodiments multiple modular generators may be distributedaround a secondary moderator surrounding a central chamber holding asubject for treatment, providing an alternative to a completelyintegrated multi-ion beam system, and may have particular benefits insome circumstances. Benefits might include (1) an ability to quicklyreplace a single generator that has failed and needs repair; and (2) anability to change alignment of the generators relative to one another,the moderator, and the subject. In regard to a subject, alignment of thegenerators may optimize dose distribution and density of neutrons at acancer site, while at the same time minimizing spurious radiation, suchas gamma rays that might be emitted external to the apparatus, or intohealthy tissue of the subject.

In the prior art, where reactor and accelerator neutron sources areused, careful attention has been given to achievement of high qualityneutron beams to meet the IAEA standards for BNCT developed in 2001 forInternational Atomic Energy Agency (IAEA) (Current Status of NeutronCapture Therapy (2001) IAEA-TECDOC-1223. In embodiments of the presentinvention, where multiple modular DD fusion generators are used, thesestandards may be relaxed. The IAEA specification assumes that there is asingle neutron beam that is used for all cancers and body locations.This results in standard values for the three neutron energies(thermals, epithermal and fast neutrons). Moderator and neutron spectralshifters are then designed to achieve these values for a particular fastneutron source as an input specification. This results in designs in theprior art that may not use the available fast neutrons economically andthen may waste some of them to achieve the IAEA universal specs. Forgenerators such as the DD fusion source in an embodiment of the presentinvention, early calculations have indicated that a single DD fusiongenerator would have difficulty achieving required fast neutron input tothe moderating process. So, in embodiments of the invention, the use ofmultiple generators increases the total fast neutron yield available andallows the moderated dose to be distributed over a larger area of thebody, instead of having the beam enter at one location of the body. Forexample, as shown in FIG. 13D, neutrons n are entering the head frommany directions. This permits reduction of thermal neutron flux at anyone point on the skin of the head while still achieving adequateepithermal flux to the cancer site. In early prior art reactor BNCTexperiments, the thermal neutron flux burned the skin of subjects.

When considering neutrons used for a particular cancer it is desirableto direct the maximum flux to the cancer site, and therefore, one mustconsider the specific cancer that is to be treated. This includeslocation and depth in the human body. Because of their relatively smallsize and large neutron yield, the modular generators in the embodimentsof the present invention are particularly able to accomplish this bybeing positioned to maximize their flux at the cancer site.

Since in embodiments of the invention generators are placed as close tothe patient's body as practical to maximize flux at the cancer site,there is a more holistic problem. There are multiple parameters for eachmodular generator: (e.g. neutron flux, neutron energy, position relativeto the body). What comes out of a single neutron beam pipe (1998 IAEAStandards, Table I) is not the only concern. A body part can now, in newimplementations of the invention, be irradiated in all directions, andneutron intensity can be adjusted at each modular generator to achievebetter flux and even more optimum neutron energy than with a single beamLINAC or a reactor. The direction of each neutron beam can be adjustedby rotating and displacing each modular generator 118. Each modulargenerator's yield can be adjusted electronically by varying theaccelerator voltage and the ion beam current. Since the moderator sizeis relatively small and compact compared to the prior art, the neutronspectrum of each modular generator 118 can be adjusted by the selectionof different moderator materials and thicknesses.

Lowering of Required Beam Quality

In embodiments of the present invention the subject's body is bombardedwith neutrons from multiple directions. The neutrons can come from allsides of the body part, which minimizes the amount of distance each beamhas to transverse. Unwanted neutrons striking the skin are nowdistributed over a larger area, reducing the skin dose of harmfulcomponents (e.g. gammas, and thermal and fast neutrons) per unit area.These components are simply delivered over a larger area of the skin.This permits adjustment of dose at the cancer site to be higher thanthat achieved with a single beam but with reduction of harmfulcomponents over a larger area of the skin.

For a single beam case in the prior art, an argument might be made thatone can rotate the patient for each exposure, but, due to possiblepatient movement, the neutrons would not be as accurately placed as inmulti-beam embodiments of the present invention. For each placement thepatient would have to be carefully re-oriented relative to the singleneutron beam, which requires careful placement of the patient.

In embodiments of the invention, multiple beam directions and an abilityto adjust the neutron flux of each modular generator allow for optimumdelivery to the cancer site while reducing harmful components. Forexample, if the cancer is located in the left lobe of the brain, theneutron flux to the tumor can be adjusted to deliver epithermal neutronsin the direction of that tumor. Since each modular generator neutronflux can be adjusted quickly by varying the accelerator's high voltageor the ion beam current, and by translation and rotation, this can bedone easily with delivery determined by a computer program. In thepresent invention, a control computer monitors the ion beam current, theacceleration voltage and the output neutron yield, which can beautomatically adjusted.

Small modular generators in embodiments of the invention can make use ofnew boron drug delivery methods for higher concentrations of boron tothe cancer sites. Higher concentrations of boron lower the requiredneutron dose and require shorter delivery time. Higher boronconcentrations to the cancer site permit use of neutron generators withlower neutron yield such as the modular DD fusion generators inembodiments of the present invention.

Each modular generator 118 is an independent device capable of producingneutrons independently of the other generators. This allows the totalavailable power, P, to be distributed over N generators, resulting inthe heat load being distributed safely without, for example damaging thetitanium targets (unlike single target devices using lithium). In oneexample there are six modular generators, distributing total heat loadper titanium target, since the number of neutrons per unit area is fixedby the ion beam power per unit target area.

To properly treat a tumor in a subject, a large number of neutrons isrequired. For reasons of temperature management and stability, DD fusiongenerators are at present limited to fast neutron yields of less than4×10¹⁰ n/sec. To increase the neutron yield, the number of neutrongenerators can be increased in embodiments of the present invention.Pre-moderators 108 can be shaped so that larger numbers of modulargenerators may be fitted around a subject to be treated. In the exampleshown by FIG. 13A there are six generators arranged equally spacedaround a common secondary moderator 112, the subject cavity 116 and thesubject 134. Spacing blocks 128, composed of moderator material that maybe the same as that of pre-moderator 108 (e.g. Teflon or polyethylene),are placed between each pre-moderator to provide adequate spacing forfitting the subject cavity 118. The wedge angle, α, as indicated in FIG.12A, on the pre-moderator in FIG. 13A determines the number of modules118 with pre-moderators 108 that can fit in the circle around thepatient and how close the sources may be to the patient. For example, awedge angle of α=30° for 6 generators and α=22.5° for 8 generators.

Moveable Sources with Fluid Moderator

One embodiment of a system of modular generators is shown in FIGS. 13Aand 13B. In FIG. 13A a plane view of six modular neutron generators 118fitting into the cylinder (or ring) is shown. In FIG. 13B, a perspectiveview is shown. The modular generators can also be arranged in otherpatterns to maximize the dose in particular locations in the subject'sbody and deliver cancer therapy to selected body organs. In someembodiments of the invention the modular generators may be moved byelectric motors and mechanical means to optimized locations to providethe maximum dose to the cancer site and tumor profile as determined byboron bio-distribution test biopsy and pathological analysis, PositronEmission Computed Tomography (PET-CT), Computed Tomography (CT) ormagnetic resonance imaging (MRI).

One may make use of moderating materials between movable modulargenerators. For clinical systems there should be moderator materialbetween the modular generators. Ideally the material can quicklyposition itself to the new location of the modular generators and alsobe a moderating material. As shown in FIG. 13D, liquid moderator 156 canbe used to surround the modular generators 118, acting as a secondarymoderator. The moderating material is shown between the movable modulargenerators. The liquid is contained in an appropriate liquid container.Liquids that also have good moderating properties can be used and areeasily displaced by the modular generators when moving. For example,different grades of 3M™ Fluorinert™ Electronic Liquid (e.g. FC-40),which is non-conductive, thermally and chemically stable fluid, can beinserted between generators. Like Teflon it contains primarily fluorineatoms, making it an excellent moderator, and no hydrogen.

Stages of Moderation

Use of multiple modular generators in embodiments of the inventionpermits efficient use of modulator material, reducing size of moderatorand shielding material and, thus, the reduction and size of the entiresystem. It also reduces the required flux density of fast neutrons bybringing the neutron sources closer to the patient and directing thelimited number of neutrons to the cancer site in a more efficientfashion. The subject's body also becomes part of the equation of themoderating process. The fact that the neutrons are coming from multipledirections reduces local skin dose and localized body dose of healthytissue. Rather than coming into the body at one location, the neutronsare coming from roughly 360 degrees around the body.

Moderation of fast neutrons in embodiments of the invention is athree-step process. In a first step (1) the pre-moderator 108 acts toreduce energy of the fast neutrons in as short a distance as practicalwith a minimal amount of gamma radiation produced in the process. Thepre-moderator also serves as a medium to (2) transport high voltage and(3) cooling fluid to a fast neutron production titanium target 106.Combining these three functions ((1) moderation, (2) fluid transport and(3) high voltage transport) reduces distance and the amount of materialbetween the fast neutron source and the patient, helping to maintain amaximum neutron flux finally delivered to the patient. Partially slowedneutrons can then pass into the secondary moderator 112 which continuesthe slowing process without undue production of gamma rays from, forexample, hydrogen. In the case of small animal models, the selectedmoderator may be heavy water (D₂O). Neutron energy reduction iscontinued by the D₂O without the generation of ˜2.2 MeV gammas thatwould occur if materials composed of hydrogen were used.

For the case of irradiating tumors of depth greater than 3 cm in a humanbody, the neutrons need to be moderated to epithermal neutron energies.The human body also acts as a partial, final moderator. Thus, theepithermal energy neutrons are slowed further as they move through thebody, and finally are slowed to thermal energies at the tumor site.Those skilled in the art will understand that the moderation is astatistical and random process that reduces the neutron energy with avariation or spread of the neutron energies. The process can also resultin undesired gamma ray components (e.g. 2.2 MeV gammas from hydrogencapture of neutrons) which damage health cells. In embodiments of theinvention, selection of the moderator material depends at least in partupon the desired energy of the neutrons at the body's skin to achievemaximum penetration to the cancer site while reducing (1) excess thermalenergy components at the skin, (2) the cost and availability of themoderator material, and (3) harmful gamma ray components. Eachgenerator's energy, yield, direction and moderation can be determinedfrom moderation materials, the generator's voltage and accelerationcurrent. Unlike in the prior art, dimensions of the moderator andcontent may be quickly changed. In some embodiments of the invention aliquid moderator (e.g. Fluorinert FC40) or a granular (e.g. AlF₃)moderator may be used. The modular generators are positioned in theliquid or granular moderator material, where they are free to move bymechanical means quickly between different cancer sites. In the priorart, the moderators and shields are large, massive and usually fixedrelative to a single beam reactor or linear accelerator. The patient isusually moved relative to the fixed neutron source.

Using liquid or granular moderator materials permits a more efficientreduction of fast neutrons to epithermal energies while minimizingthermals and fast neutrons. Selection of the pre-moderator material isimportant for optimum neutron beam quality. Generally speaking, beamquality involves minimization of harmful components of radiation thataccompany the production of thermal neutrons at the cancer site but alsothe minimization of the fast and thermal neutrons at the skin surface.In this process gamma rays are produced and, depending upon the cancersite, fast neutrons must be converted to the right energy so that theypenetrate the body and deliver thermal neutrons to the tumor site withminimal irradiation of healthy tissue.

Moderating the neutrons to thermal energy can result in the skin beingdamaged. Indeed, the thermal neutron dose to the skin can be larger thanthe dose to the tumor. The body itself moderates and absorbs theneutrons as they penetrate the body. Selection of the moderator materialrequires materials that do not moderate the fast neutrons too quickly tothermal energies. Thermal neutrons can damage the skin, and if hydrogenatoms are present in the moderation process, then damaging gamma raysare also produced. Like the moderator, the human body also moderates andabsorbs the neutrons. The desired required depth of penetration dependsupon the location of the tumor in the body. Simulations show thatpenetration of thermal neutrons starting at the skin results inpenetration depths of 3 to 5 cm before a large fraction of the neutronsare absorbed.

Teflon Moderator for Clinical Machine

When used as a Pre-moderator, Teflon (PTFE) can satisfy 6 of the 7functions listed above. Indeed, on several of the attributes Teflonexcels. For example, since Teflon does not have atomic hydrogen, gammaproduction is avoided, whereas the use of HDPE does have hydrogen and,therefore maximizes the thermal neutron moderation with and added 2.2MeV gamma ray component. Selection of HDPE as the pre-moderator materialresults in production of thermal neutrons in a short distance from theTi target, whereas the use of Teflon results in a slower rate of neutronenergy reduction from 2.5 MeV permitting the production of epithermalneutrons for deeper penetration into the human body and no 2.2 MeVgammas.

Teflon can have a minimum high voltage in which surface arcs (flashoversor surface discharges) momentarily short out the high voltage, and leadto damage to the Teflon surface and possibly damage to the high voltagepower supply. This is primarily a materials problem and not a structuralproblem (shape of the accelerator and Teflon shape and structure).Surface discharge along solid insulators in a vacuum in high voltagedevices determines the maximum voltage between an anode and a cathode.The voltage hold-off capability of a solid insulator in vacuum isusually less than that of a vacuum gap of similar dimensions. O.Yamamoto et. al (Yamamoto, O; Takuma, T; Fukuda, M; Nagata, S; Sonoda, T“Improving withstand voltage by roughening the surface of an insulatingspacer used in vacuum,” IEEE TRANSACTIONS ON DIELECTRICS AND ELECTRICALINSULATION (2003), 10(4): 550-556) has studied a simple and reliablemethod to improve surface insulation strength of a dielectric such asTeflon, PMMA, and SiO₂ by roughening the surface of the dielectric. Someexperimental results have revealed that in a vacuum, charging along thesurface of an insulating spacer precedes the flashover. The chargingtakes place through a process in which electrons are released from atriple junction where the cathode, insulator and vacuum meet, andpropagate toward the anode, causing a secondary emission electronavalanche (SEEA) along the insulator surface. The dielectric (e.g.Teflon or HDPE) can hold charge like a battery or capacitor and thenrelease it along the surface. This limits the use of plastics such asTeflon and HDPE as insulators and moderators inside the vacuum chamberof the neutron generator's acceleration chamber 100.

For short distances across Teflon (10 mm), Yamamoto found that roughingthe surface (e.g. with sandpaper or sandblasting) affects the chargingof various plastics (such as Teflon and HDPE), which decreases asroughness increases. Yamamoto used roughness up to 37.8 μm but had usedlower voltage gradients and smaller dielectric thicknesses (10 mm).Studies in embodiments of the present invention find that largersurfaces (distances e.g. 8 inches) of Teflon can be roughened withroughness values of 5 microns and greater and achieve high voltages of150-220 kV for distances greater than ˜2 cm without flashover.

More importantly, the roughing method gives higher insulation strengthswithout time-consuming conditioning previously used. This provides asignificant advantage and makes generators in embodiments of the presentinvention operational more quickly.

Depending on maximum field strength required, conditioning by theroughing process could take minutes or days. Below 1 MV m⁻¹, theconditioning process is relatively fast. Between 1 and 10 MV m⁻¹, theconditioning process takes longer. The best way to monitor howconditioning is going is to record the number of transient discharges(or sparks) per hour. At very high fields the arc rate might never getbetter than a few arcs per hour. A tolerable arc rate depends on theapplication. If no high voltage breakdown (arcs) can be tolerated, thenthe system must first be conditioned to a higher field, and then whenthe voltage is reduced to the operating level the arc rate drops almostto zero. For very high field strengths above 10 MV m⁻¹, it is verydifficult to condition the electrodes to give an arc rate of zero. Theelectrode shape and material composition becomes very important at thesefield levels.

The Importance of the Human Body in the Moderation Process

The human body acts as a moderator to reduce the epithermal neutrons tothermal energies at the cancer site. The amount of neutron energyreduction by the human body depends at least in part upon the depth ofthe tumor in the body. This determines the maximum neutron flux fordelivery to the patient. The desired reduction of the neutron's energywill depend upon the depth of the tumor in the human body. For example,with throat and neck cancers the reduction of the neutron energy tothermal energies is desired for maximum dose to the cancer site. Forsmall animal models, thermal energies are also desired.

Dimension in the body from the skin (epidermis) to the cancer site canvary, requiring the neutron energy to be large enough for penetration tothe cancer while still primarily at thermal energies, permitting captureby the boron and the destruction of cancer cells. For small animalmodels or skin cancer in humans, the neutrons can be at thermalenergies. For cancers at deeper depths in the body, epithermal neutrons(0.025 to 0.4 eV) can be used.

For deep tumors in the torso, such as, for example, pancreatic tumors,epithermal neutrons are required. Pancreatic tumors are deep in thetorso and require epithermal neutrons at entrance to the body topenetrate to the tumor. Moderation of the epithermal neutrons occurs asthey pass though the body. Simulations in various embodiments show thatthere are materials at the right thicknesses, such as Teflon, ⁷LiF andAlF₃, which produce the epithermal neutrons that penetrate the body andthermalize by the time they reach the depth of the tumor with a maximumneutron flux. In embodiments of the invention, this occurs whileminimizing production of thermal neutrons at the skin.

Shape of a Clinical Machine to Match a Human Body

The shape of the patient's chamber in a machine may be contoured to fitthe human body part to maximize radiation to the cancer site. The shapedepends upon the body part to be irradiated and the location of thetumor. As shown in FIG. 13D, for glioblastoma 148 (brain cancer),modular generators 118 may be arranged in a close ring around the head146 that maximizes neutron flux to the cancer site 148 in the brain. Theintensity of each generator can be varied to achieve maximum thermalneutrons to the tumor while minimizing the dose to healthy tissue. Asdiscussed above, applications in embodiments of this invention permitcontrol of the distance of each generator from the cancer site. Thecancer site may be mapped using radiographic means (CT scans) and/orMRIs. A treatment planning protocol can then be determined for theoptimum use of the clinical neutron source. The intensity of theneutrons coming from each neutron generator can then be varied and thelocation of each individual generator can be optimized.

As shown in FIG. 13 D, an improvement of the moderator surrounding themodular generators is to suspend or surround the modular generators witha liquid 156 that does not contain hydrogen (a gamma producing source),but has modest atomic-number atoms like Fluorine, Carbon or Nitrogen.Various kinds of Fluorinert (tradename), FC-70 or FC-40, or FC3839 canbe used. The fluid may be put between the modular generators and bymechanical means each modular generator can move independently of theother generators to a certain extent. This fluid can also absorb someheat from modular generators.

As shown in FIG. 13 D, an improvement of the moderator surrounding themodular generators is to suspend or surround the modular generators witha liquid 156 that does not contain hydrogen (a gamma producing source),but has modest atomic-number atoms like Fluorine, Carbon or Nitrogen.Various kinds of Fluorinert (tradename), FC-70 or FC-40, or FC3839 canbe used. The fluid may be put between the modular generators and bymechanical means each modular generator can move independently of theother generators to a certain extent. This fluid can also absorb someheat from modular generators.

Generator Alignment

In embodiments of the present invention each stand-alone generator, asseen in FIG. 13D, for example, may be positioned and aligned to give amaximum flux and neutron distribution at the cancer site. Each generatoris small enough in size and weight that the generators may bemechanically moved and positioned so that optimum neutron flux at thecancer site is achieved, depending upon the cancer's location anddistribution. The generators may be arranged around a moderator whoseradial thickness is optimized to deliver a maximum thermal neutron fluxto the cancer site. Depending upon the body part being irradiated, thegeometry can be circular or elliptical. By selecting the moderatingmaterial and radial thickness one can deliver thermal neutrons to thecancer site.

FIG. 14A shows an on-axis view of an exemplary clinical neutron sourceusing multiple modular generators 118 for BNCT of a human head. Thisexample uses eight modular generators 118 and assorted moderatormaterials coupled with reflecting and shielding material (e.g. graphite144). Secondary moderators (166 and 170) can be composed of one or morematerials. There are moderator spacing blocks 128 in one embodimentcomposed of the same material High Density Polyethylene (HDPE), UltraHigh Molecular Weight polyethylene (UHMW), or (PTFE (Teflon)) as thesecondary moderators. Blocks of these materials fit in between themodular generators and are adjacent to each generator's pre-moderator.They act as mechanical spacers as well as moderator components. Theoutside of this region, between and behind the modular generators 118,is filled with either graphite or lead 144 to serve as a neutronreflector and shield.

FIG. 14B also shows a side section view of the apparatus of FIG. 14Ataken along a line through the top and bottom generators. There isadditional moderator material in the front and behind the modulargenerators, extending a little above the pre-moderator. In our example,the cylindrical space 164 available for the patient's head is 52 cm deepand 30 cm in diameter. This space might be lined with 1-mm of cadmium162 to shield against too large a thermal neutron dose to the patient'sskin. Shield 162 is also shown in FIG. 14A. In other embodiments thisspace may be lined with ⁶LiF.

The exemplary arrangement as illustrated in FIGS. 14A and B has asecondary moderator consisting of multiple layers of 40% Al and 60% AlF₃(166) and an additional moderating cylinder 170 of either ⁷LiF or D₂O.These materials are shown to be concentric rings in FIG. 14A. Since ⁷LiFor D₂O can be expensive, thicknesses were varied to obtain a desiredneutron beam quality without over-using either ⁷LIF or D₂O. In theexample shown in FIGS. 14A and 14 B the thickness ratio between the twosegments is altered, the total moderator thickness is 34 cm, and thesources are R=52.5 cm from the origin (center of the brain). The effectof doing this varying these materials is plotted graphically in FIG. 15.

The reflector material graphite 144 is 30 cm thick in this example, thethickness of the Teflon 168, t, in front of the 2.5 MeV source isvaried, and the portion 170 of the moderator is either ⁷LiF or D₂O. As tchanges, the thickness of the Al/AlF₃ 166 of the moderator changes, withall other dimensions remaining constant. The target is embedded in theTeflon 168, UHMW or HDPE. Sources are titanium targets 106 beingbombarded by deuterium ion beams 5.0 cm in diameter. Each target isemitting 4×10¹⁰ neutron/sec. Eight modulator generators 118 emit3.2×10¹¹ n/s total emission.

A concentration of ¹⁰B in the tumor and health tissue (e. g. skin) isknown to be possible. ¹⁰B tumor concentration is assumed to be 50 ppm,while ¹⁰B in healthy tissue is 15 ppm. The relative biologicaleffectiveness (RBE) for ¹⁰B in tumor is 2.7, and in healthy tissue is1.3. Tumor and healthy tissue doses are calculated using the NRC andICRP models for neutron RBE. The material ⁷LiF was the best performerand D₂O was second best.

An important main objective in these examples is to give a sufficientdose of neutrons to the cancer while minimizing the dose to the healthytissue and not damaging it. FIG. 15 shows the performance for moderatorswith different values for tin cm and either ⁷LiF or D₂O in the secondarymoderator. The ordinate R is the ratio of tumor dose at the origin tohealthy tissue skin dose, and the tumor dose at the center of the brainassumed to be the site of the cancer. As can be seen from FIG. 15, ⁷LiFoutperforms D₂O. The best performance is R=1.9 and a tumor dose inexcess of 1.4 Sv/hr. A consequence of RBE is that a small percentage offast neutrons is essential to obtain a high value for R; also, areasonable number of epithermals is required to penetrate the target.Thus a combination of ⁷LiF and D₂O may outperform either material alone.

A Need for Small Animal Neutron Sources

Development of boron delivery agents for BNCT is an ongoing andchallenging task of high priority. A number of boron-10 containingdelivery agents have been prepared for potential use in BNCT. With thedevelopment of new chemical synthetic techniques and increased knowledgeof the biochemical requirements needed for an effective agent and theirmodes of delivery, a wide variety of new boron agents has emerged, butonly two of these, oronophenylalanine (BPA) and sodium borocaptate (BSH)have been used clinically and have US FDA approval. Patient-derivedxenograft (PDX) is created by transferring primary tumors from a patientinto a mouse or small animal model. Tests of delivery and effectivenessof drugs to the cancer site can then be performed. In the prior art,only beamlines from nuclear reactors and linear accelerator structurescan be used. A small laboratory neutron source, as in embodiments ofthis invention, is therefore valuable in the development and testing ofnew boron delivery drugs and their effectiveness in destroying thecancer site.

As compared to a clinical delivery system, a smaller number ofstand-alone generators such as generators 118 is needed for a deliverysystem for a small animal such as a mouse. The modular generators usedhave a slab wall angle of α=0 (see α defined in FIG. 12 A). Thesecondary moderator may be a separate container of heavy water (D₂O).

Since the small animal target is indeed small, the secondary moderatorvolume can be reduced, and the compact modular generators can be movedclose to it permitting the modular generators to be closer to the animaltarget. Thus, the neutron flux at the cancer site is increased, and withproper selection of moderator material and size, will still be able tomoderate the neutrons to IAEA standards. In addition, by moving closer,the number of generators can be reduced while still maintaining a highthermal neutron flux at the cancer site.

In our example of the new art for a small animal source, we can use fourmodular generators 118 to emit enough thermal neutrons at the cancersite. We can use the modular generators of 12 A, B, C with the slab wallangle of α=0. This makes the pre-moderator 108 a rectangular cuboid (or“rectangular slab” of). FIG. 16A is a perspective view of a modulargenerator having such a rectangular pre-moderator 108, making itsuitable for arrangements of four generators in a rectangular array, asshown in FIG. 16B. In FIG. 16B the four modular generators are arrangedaround a secondary moderator 112, which in one embodiment may be acontainer of heavy water or granulated moderator material. FIG. 16C is across section view of the arrangement of FIG. 16B, taken along sectionline4 16C-16C of FIG. 16B. The elements previously annotated for modulargenerators are reused in FIGS. 16 A, B and C.

FIG. 16D is an exploded view where the four generators 118 are movedback from the small heavy water moderator 112. Each generator 118 has apre-moderator 108 with a fast neutron generator with a titanium target106. A deuterium ion beam is generated by a plasma ion source 102 andaccelerated in an acceleration chamber 100 to the titanium target 106,where the DD fusion reaction occurs releasing fast 2.5 MeV neutrons.This description is all common to the descriptions or other embodimentsin the specification. The neutrons generated pass through apre-moderator 108, where they are partially moderated to thermal neutronenergies. They then pass into the moderator block 112 where they arefurther moderated, reducing the energy of fast neutrons to thermalneutron energies. The thermal neutrons then enter a cylindrical mousechamber 114 where they enter the small animal 116.

The pre-moderator is designed to slow the fast neutrons to thermalneutrons by scattering the fast neutrons via collisions with thehydrogen in the HDPE or UHMW plastics. The distance the 2.5 MeV neutronshave to traverse is approximately 3 to 5 cm, wherein approximately 50%of the neutrons lose enough of their energy to be classified as thermalneutrons. These neutrons, containing both thermal and fast neutroncomponents, can then travel into the moderator box 112, where they arefurther moderated by collisions with deuterium atoms. Roughly speaking,the HDPE with its hydrogen-atoms moderates the neutrons to thermalenergies over a short distance; the thermalized neutrons then penetratethe cylindrical chamber 114 wherein they place the small animal 116. Thesmall animal model is used to test the delivery of boron to the cancersite.

For the pre-moderator, high density polyethylene (HDPE) is optimum forproducing the maximum flux of thermal neutrons. As in the case of theclinical generator, it is desired to produce a maximum thermal flux atthe cancer site. A mouse is a small object, and penetration of thermalneutrons to the cancer site can easily be achieved. Moderation of thefast neutrons to thermal energies is desired with minimum production ofgamma radiation, which is harmful to the healthy cells. As those skilledin the art will understand, hydrogen atoms are excellent at scatteringfast neutrons, resulting in moderation of the neutrons to thermalenergies in the shortest path length in the moderating material. Indeed,using 5-6 cm of high-density polyethylene (HDPE) or UHMW plastic resultsin moderation of about 50% of 2.5 MeV neutrons to thermal energies.Further moderation of the neutrons by longer distances in the HDPEresults in more fast neutrons being converted to thermal energies.However, this results in reduction of the total flux (n/cm²) that isavailable since the neutrons are being emitted in a 4π solid angle.Hydrogen capture of neutrons produces high energy gamma radiation, whichis destructive to both healthy and cancerous cells. Adding anothermoderator to further thermalize the neutrons is accomplished by the useof heavy water (D₂O).

The skilled person will understand that the embodiments described inthis application are exemplary, and not limiting. Many variations maywell fall within the scope of the invention, which is limited only bythe scope of the following claims.

What is claimed is:
 1. A Boron neutron cancer treatment system,comprising: a secondary moderator having a central treatment chamber fora subject; and six neutron generators, each comprising a pre-moderatorblock of moderating material having an upper surface, a lower surface, afirst and a second end, opposite side surfaces angled inward by thirtydegrees along at least a portion of the height, a first length, a firstwidth less than the first length, and a first thickness, a cylindricalacceleration chamber having a first diameter the first width of thepre-moderator block, sealed at one end to the upper surface of thepre-moderator block adjacent the first end of the pre-moderator block,with a vertical axis perpendicular to the upper surface, theacceleration chamber having a height and a top cover at a second endaway from the pre-moderator block, a vacuum pump engaging theacceleration chamber at a right angle to the vertical axis, evacuatingthe acceleration chamber to a high vacuum, a plasma ion chamber openinginto the acceleration chamber through an ion extraction iris through thetop cover of the acceleration chamber on the vertical axis of theacceleration chamber, a gas source providing deuterium gas to the plasmaion chamber, a microwave energy source ionizing the gas in the plasmaion chamber, a cylindrical primary isolation well extending a distanceinto the pre-moderator block from the upper surface, centered on thevertical axis of the acceleration chamber, a secondary isolation well ina shape of a hollow cylinder surrounding the primary isolation well, toa depth somewhat less than the distance of the primary isolation well,within the first diameter of the acceleration chamber, a water-cooledtitanium target disk having a target surface orthogonal to the axis ofthe acceleration chamber, the target disk having a diameter smaller thena diameter of the isolation well, positioned at a lower extremity of theisolation well, the target disk biased to a negative DC voltage, andelectrically grounded metal cladding covering all otherwise exposedsurfaces of the pre-moderator block; wherein the six neutron generatorsare positioned around the secondary moderator with the axis of eachacceleration chamber passing through the center of the treatmentchamber, and with the angled sides of the neutron generators fullyadjacent.
 2. The system of claim 1 further comprising six rectangularspacing blocks of moderator material, one spacer block placed betweeneach adjacent neutron generator with sides of the spacer blocks fullyadjacent with the angled sides of the neutron generators.
 3. The systemof claim 1 wherein the secondary moderator is shaped to fill all volumebetween the neutron generators and the central treatment chamber.
 4. Thesystem of claim 1 wherein the secondary moderator is a block or blocksof solid moderator material.
 5. The system of claim 2 wherein thesecondary moderator is a container filled with heavy water.
 6. Thesystem of claim 2 wherein the secondary moderator is a container filledwith granulated moderator material.